Conformational analysis of diols: Role of the linker on the relative orientation of hydroxyl groups

Article abstract of DOI:10.1002/poc.3975

Conformational flexibility of three covalently linked alcohol dimers, composed of xanthenol units and diphenyl ether (DPE(OH)₂), 9,9-dimethylxanthene (XAN(OH)₂), or biphenyl (BP(OH)₂) linkers was studied. The relative orientation of the two alcohol units (In-In, In-Out, and Out-Out conformers) in the model compounds was investigated using NMR spectroscopy, X-ray crystallography, and density functional theory (DFT) calculations. Diols containing rigid linkers, such as XAN(OH)₂ and BP(OH)₂, favor the formation of an In-In conformer in solution, and the interconversion between different conformers was slow on the NMR timescale. Interestingly, XAN(OH)₂ adopted an In-Out conformation in the crystalline solid state, possibly due to additional intermolecular interactions. More flexible DPE(OH)₂ was found to freely interconvert on the NMR timescale. This study provides important structural information that can be utilized in catalysis, metal-ligation, and other applications.

Full text of DOI:10.1002/poc.3975

Received: 19 February 2019
DOI: 10.1002/poc.3975
Revised: 15 April 2019
Accepted: 1 May 2019
R E S E A R C H A R T I C L E
Conformational analysis of diols: Role of the linker on the
relative orientation of hydroxyl groups
1
,2
1,2
3
1,2
Marija R. Zoric
| Varun Singh
| Matthias Zeller | Ksenija D. Glusac
1
Department of Chemistry, University of
Illinois at Chicago, Chicago, IL
Abstract
2
Conformational flexibility of three covalently linked alcohol dimers, com-
posed of xanthenol units and diphenyl ether (DPE(OH)2), 9,9‐
dimethylxanthene (XAN(OH) ), or biphenyl (BP(OH) ) linkers was studied.
Chemical Sciences and Engineering
Division, Argonne National Laboratory,
Lemont, IL
2
2
3
Department of Chemistry, Purdue
The relative orientation of the two alcohol units (In‐In, In‐Out, and Out‐
Out conformers) in the model compounds was investigated using NMR
spectroscopy, X‐ray crystallography, and density functional theory (DFT) cal-
culations. Diols containing rigid linkers, such as XAN(OH) and BP(OH) ,
University, West Lafayette, IN
Correspondence
Ksenija D. Glusac, Department of
Chemistry, University of Illinois at
Chicago, Chicago, IL 60607.
Email: glusac@uic.edu
2
2
favor the formation of an In‐In conformer in solution, and the interconver-
sion between different conformers was slow on the NMR timescale. Interest-
ingly, XAN(OH) adopted an In‐Out conformation in the crystalline solid
2
Funding information
National Science Foundation, Grant/
Award Numbers: CHE 0087210 and CHE‐
state, possibly due to additional intermolecular interactions. More flexible
DPE(OH)2 was found to freely interconvert on the NMR timescale.
This study provides important structural information that can be utilized in
catalysis, metal‐ligation, and other applications.
1565971; Youngstown State University;
Ohio Board of Regents, Grant/Award
Number: CAP‐491; Ohio Supercomputer
Center
KEYWORDS
conformation, dimer, interconversion, covalently linked dimers, conformational analysis
1
| INTRODUCTION
perylene‐diimide dimers were prepared using linkers
composed of the xanthene moiety, and longitudinal dis-
Chemists often resort to the covalent linking of molecular
units to bring two reactive moieties into a desired geome-
try or to eliminate the effect of molecular diffusion on
reaction kinetics. For example, covalently linked dimers
were utilized in singlet fission, a process in which the
singlet excited state, localized on one of the chromo-
phores, is split into two triplet excited states localized
placement groups composed of phenyl‐acetylides were
used to investigate the effects of slip‐stacking on the
degree of excitonic coupling.
[
4]
In catalysis, covalently linked dimers play an impor-
tant role of bringing reactive groups into a desired
orientation. For example, the reduction of molecular oxy-
gen to water requires a proton‐coupled four‐electron
reduction, demanding catalytic metal centers capable of
accumulating these redox equivalents. Such burden on a
single metallic center can be lowered using covalently
linked bimetallic catalysts that share the number of redox
equivalents needed for oxygen reduction. For instance,
face‐to‐face bis‐cobalt porphyrin catalysts were prepared
using spacers of varying length to determine the optimal
distance needed for the four‐electron reduction
[1,2]
on two chromophores.
These studies involved a
photophysical investigation of tetracene and pentacene
dimers connected covalently by o,m,p‐substituted ben-
zene and xanthene linkers, with the aim of identifying
the ideal dimer geometry that maximizes the coupling
matrix element for singlet fission. Similarly, covalently
linked dimers were synthesized to investigate J‐ and H‐
[3]
type aggregates. For example, a series of slip‐stacked
J Phys Org Chem. 2019;e3975.
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© 2019 John Wiley & Sons, Ltd.
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https://doi.org/10.1002/poc.3975

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ZORIC ET AL.
[
5–8]
catalysis.
Interestingly, these studies showed a poor
alcohol moieties using X‐ray crystallography, NMR spec-
troscopy, and density functional theory (DFT) calcula-
tions. The results of our work are relevant for potential
use of these diols in catalysis and other applications.
correlation between metal‐metal distances and catalytic
performance, indicating more complex effects dominat-
ing catalysis kinetics. A similar bimetallic catalysis
approach has been utilized to accelerate an oxygen evolu-
tion reaction. Ru‐based dimers were prepared using
several linkers of varying length, and the best catalytic
performance was observed in dimers with flexible linkers
that can accommodate varying Ru‐Ru distances needed
[9]
2
| EXPERIMENTAL SECTION
.1 | General methods
[10]
for different steps of the catalytic cycle.
2
Our group is interested in metal‐free motifs capable of
catalyzing electrochemical oxidation and reduction reac-
All reagents and starting materials were purchased from
commercial sources and used as received without purifi-
[11–16]
tions.
In our studies of the oxygen evolution reaction
(
OER), catalytic behavior was observed in an electrode‐
cation, unless specified otherwise. 9‐Phenylxanthen‐9‐ol
1
assisted mechanism, where selected electrodes, such as
glassy carbon and platinum, exhibited improved oxygen
evolution performance in the presence of iminium or
oxonium cations.
size that a fully homogeneous catalyst, composed of
(
MONO(OH)) was purchased from TCI America. H,
13
C, COSY, HSQC, and HMBC NMR spectra were col-
lected using a spectrometer operating at a field of 11.7 T
[14–16]
1
13
These results lead us to hypothe-
(
500 MHz for H and 125 MHz for C, Bruker‐
Spectrospin 500 Ultra Shield). Spectra are described
through chemical shifts, multiplicity (s, singlet; d, dou-
blet; t, triplet; q, quartet; m, multiplet), coupling constant
in hertz (Hz), number of protons, and assignments of pro-
tons (or carbons, atom labels are presented in Scheme 1).
MALDI spectra were collected on a Bruker Drucker
Daltonics Omniflex mass spectrometer. UV‐vis absorp-
+
covalently linked organic cations (R , such as iminium
and oxonium ions), can catalyze the water oxidation
process via alcohol (R‐OH) and peroxide (R‐O‐O‐R)
intermediates, by the following sequence: (a) 2R
+
+
+
+
2H O 2ROH + 2H ; (b) 2ROH RO‐OR + 2H
2
− −
+
+
2e ; (c) RO‐OR O + 2R + 2e . The critical and
2
most challenging step in this catalytic sequence is the for-
mation of peroxide via oxidative O─O bond coupling of
two alcohols. Given high reactivity of O‐centered radicals,
it is important to design appropriate linkers that can posi-
tion two ─OH groups into the required geometry for O─O
bond coupling.
tion spectra were taken on
spectrophotometer.
a
HP8453 UV‐vis
2.2 | Crystallography
This manuscript investigates conformations of three
covalently linked alcohol dimers presented in Scheme 1.
The xanthenol unit was used as a model alcohol that
can be formed by a reaction between the xanthylium cat-
ion and water. Three types of linkers were investigated,
namely, diphenyl ether, xanthene, and biphenyl. The
XAN(OH) crystals were obtained by vapor diffusion. A
2
small amount of the compound dissolved in dichloro-
methane was placed in an open vial inside a container
with pentane and kept in the refrigerator (approxi-
mately 5°C). BP(OH)2 crystals were grown by slow
evaporation of a saturated ethanol solution at room
temperature. Single crystal X‐ray structures were col-
lected on area detector diffractometers at 100 K using
monochromatic Mo or Cu Kα radiation (see the
Supporting Information Section 2 for details on data
collection and structure refinements).
conformational analysis of DPE(OH) has been reported
2
previously, and it was found that the diphenyl linker is
flexible, enabling the relatively fast rotation of two alco-
[17]
hol units.
In this work, we extend the conformational
analysis to additional model dimers, XAN(OH)2 and
BP(OH) , and investigate the relative orientation of two
2
SCHEME 1 Molecular structures of
xanthenol‐based compounds used in this
study. The numbering scheme for carbon
and proton atoms was added to aid the
NMR, X‐ray, and computational analysis

ZORIC ET AL.
3 of 9
3
3
| SYNTHESES
.1 | DPE(OH)2
H, H2′), 7.01 (t, J = 8.6 Hz, 2 H, H10), 7.09‐7.21 (m, 8
H, H2, H11, H4, H3), 7.26‐7.31 (m, 4 H, H4′, H5), 7.34‐
7.41 (m, 4 H, H3′, H5′), 7.54 (s, 2 H, OH), 7.83 (dd,
13
J = 9.3 Hz, 2 H, H9) C NMR (125 MHz, DMSO‐d6) δC
73.10 (C7), 116.15 (C4′), 116.56 (C11), 123.34
(C2′), 124.22 (C2), 125.46 (C4), 126.80 (C3), 128.99 (C8),
129.23 (C3′), 129.33 (C9), 129.35 (C5), 129.58
(C5′), 129.80 (C13), 131.19 (C12), 133.24 (C10), 141.56
(C6′), 144.87 (C6), 149.48 (C1′), 150.43 (C1).
The compound was synthesized according to a previously
[17,18]
1
published procedure.
H
NMR (500 MHz,
DMSO‐d6) δH 5.66 (d, J = 8.8 Hz, 2 H, H12), 6.02 (s, 2
H, OH), 6.87‐7.06 (m, 14 H, H2, H2′, H11, H10, H5, H4,
and H4′), 7.13‐7.18 (m, 4 H, H3′, and H5′), 7.26 (m, 2
13
H, H3), 7.53 (d, J = 7.3 Hz, 2 H, H9) C NMR
(
(
(
(
125 MHz, DMSO‐d6) δ 68.23 (C7), 116.07 (C2′), 116.64
C
+
−
C2), 118.54 (C6′), 120.93 (C12), 122.90 (C11), 123.08
C10), 127.52 (C9), 128.02 (C3′), 128.60 (C5′, C5), 128.64
C4′), 128.77 (C3), 128.80 (C6), 128.87 (C4), 138.40 (C8),
3.4 | MONO ClO4
A 20‐mL vial was charged with MONO(OH) (0.20 g,
1
49.52 (C1), 149.74 (C1′), 155.10 (C13).
0.73 mmol) and concentrated perchloric acid (70%,
5
5
mL). The resulting yellow mixture was stirred for
hours, the precipitate was filtered off, washed with
3
.2 | XAN(OH)2
diethyl ether (30 mL), and dried under reduced pressure
to give MONO ClO (0.25 g, 0.70 mmol, 96%) as a
yellow solid. H NMR (500 MHz, CD CN): δ 8.39 (dt, 2
H), 8.20 (d, 2 H), 7.99 (dd, 2 H), 7.78 (dt, 2 H), 7.69 (tt,
+
−
4
9
,9‐Dimethylxanthene (0.20 mL, 1.0 mmol) and tetra-
1
3
H
methylethylenediamine (TMEDA, 0.33 mL, 2.3 mmol)
were dissolved in 6 mL of anhydrous tetrahydrofuran
1
H), 7.63 (m, 2 H), 7.49 (m, 2 H).
(THF). The solution was purged with argon for
3
0 minutes and cooled to −78°C. A solution of n‐
butyllithium in hexane (2.5M, 1.2 mL, 3.0 mmol) was
added dropwise over a period of 5 minutes. The resulting
mixture was stirred for 1 hour at −78°C and then three
more hours at room temperature. A solution of xanthone
2
+
−
4 2
3
.5 | DPE (ClO )
The dication was synthesized according to a published
[
18]
procedure.
(
(
A 15‐mL vial was charged with DPE(OH)2
0.30 g, 0.50 mmol) and concentrated perchloric acid
70%, 8 mL). The resulting mixture was stirred overnight.
The orange precipitate that formed was filtered off,
washed with anhydrous ethyl ether (30 mL), and dried
in vacuum to give 0.36 g (0.49 mmol, 98%) of an orange
solid. H NMR (500 MHz, CD CN): δ 7.34 (d,
J = 8.6 Hz, 2 H), 7.39 (dd, J = 1.7, 7.6 Hz, 2 H), 7.49
td, J = 1.0, 7.6 Hz, 2 H), 7.60 (ddd, J = 1.0, 7.0, 8.2 Hz,
H), 7.74‐7.80 (m, 6 H), 8.33 (dd, J = 1.0, 8.8 Hz, 4 H),
.50 (ddd, J = 1.6, 6.9, 8.7 Hz, 4 H); C NMR
(
0.4280 g, 2.2 mmol) in 12 mL of anhydrous THF was
added portion wise via cannula over a period of
0 minutes. The reaction mixture was left to stir over-
1
night. The mixture was treated with saturated aqueous
ammonium chloride, extracted with dichloromethane,
washed with water, and dried over sodium sulfate. The
solution was filtered, the solvent was evaporated under
reduced pressure and the residue was recrystallized from
methanol to give 0.3580 g (0.595 mmol, 64%) of the
1
3
H
(
4
8
(
1
1
desired compound as a white solid. H NMR (500 MHz,
13
DMSO‐d6) δH 1.59 (s, 6 H, H15), 6.35 (dd, J = 7.9,
125 MHz, CD CN): δ 120.3, 121.2, 123.7, 125.4, 126.5,
3 C
30.6, 132.6, 133.2, 135.6, 146.4, 154.1, 159.6, 173.1;
MALDI: m/z = 528.33 (M ).
1
.5 Hz, 2 H, H11), 6.93 (t, J = 7.8 Hz, 2 H, H10), 7.15‐
7
.28 (m, 8 H, H2 and H4), 7.36 (m, 4 H, H3), 7.42 (dd,
+
J = 7.8, 1.5 Hz, 2 H, H9), 7.90 (dd, J = 7.9, 1.4 Hz, 4 H,
13
H5), 8.29 (s, 2 H, OH) C NMR (125 MHz, DMSO‐d6)
δC 31.7 (C14), 34.6 (C15), 72.3 (C7), 116.4 (C2), 123.5
2+
−
4 2
3
.6 | XAN (ClO )
(C10), 124.1 (C4), 125.0 (C3), 129.0 (C11), 129.4 (C5),
1
29.7 (C9), 130.1 (C6), 132.3 (C12), 135.6 (C8), 147.6
2
+
−
The same reaction procedure as for DPE (ClO ) was
+
4
2
(C13), 149.1 (C1). MALDI m/z 585 [M‐17] .
used. The product was isolated in 95% yield as a dark
1
orange solid. H NMR (500 MHz, CDCl ) δ 2.00 (s, 6
3
H
3.3 | BP(OH)2
H), 7.23 (dd, 2 H), 7.45‐7.55 (m, 6 H), 7.75 (dd, 4 H),
13
8.08 (dd, 2 H), 7.20‐7.30 (m, 8 H) C NMR (125 MHz,
The compound was synthesized according to a previously
CDCl ) δC 32.58, 34.65, 117.96, 119.31, 122.96, 124.58,
3
[19] 1
published procedure.
H NMR (500 MHz, DMSO‐d6)
129.16, 129.69, 130.72, 131.59, 132.02, 144.89, 145.00,
+
δH 6.58 (d, J = 8.0 Hz, 2 H, H12), 6.94 (d, J = 7.5 Hz, 2
157.02, 172.02. MALDI m/z 568 [M] .

4
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ZORIC ET AL.
2
+
−
3
.7 | BP (ClO )
compound for NMR studies. The synthesis of model com-
pounds was achieved by a reaction of xanthone with the
dilithiated ligand, as described in Section 2. In an initial
study, we used UV‐vis spectroscopy to investigate the
pH dependency of the interconversion between the
xanthilium cation and the corresponding pseudobase
(PB). Subsequent conformational studies were performed
using NMR spectroscopy, X‐ray crystallography, and DFT
calculations.
4
2
2+
−
The same reaction procedure as for DPE (ClO ) was
used. The product was isolated in 94% yield as a yellow
solid. H NMR (500 MHz, DMSO‐d6) δ 8.50‐8.60 (m, 6
H), 8.47 (d, 2 H), 8.35‐8.40 (m, 4 H), 8.25 (d, 2 H), 7.97
t, 2 H), 7.91 (t, 2 H), 7.70‐7.80 (m, 4 H), 7.62 (m, 2 H).
Caution: Perchlorates are strong oxidizing agents and
4
2
1
H
(
explosives.
3.8 | Computational methods
4.1 | UV‐vis absorption spectroscopy
All calculations were performed at the Ohio Supercom-
The ability of model dimers to interconvert between the
cationic (C) and PB forms was evaluated using pH‐
dependent UV‐vis absorption spectroscopy, as exempli-
fied with XAN(OH)2 in Figure 1A. The C form of
[20]
puter Center using Gaussian 09 software.
Gas phase
geometry optimizations were performed using the
[21,22]
B3LYP
hybrid functional and the 6‐311G* basis set.
Vibrational frequency analyses for the optimized struc-
tures showed the absence of imaginary frequencies for
the ground‐state structures, and the presence of only
one imaginary frequency for transition state (TS) geome-
XAN(OH) absorbs at 289 nm and is stable at neutral
2
pH values. As pH is decreased, the PB form of XAN(OH)2
is formed and can be identified by its absorption bands at
3
63 and 460 nm. The PB pK values were determined
[
23]
a
tries. The energies were calculated using the IEFPCM
from photometric titration data and were found to corre-
late with the electronic factors that affect the stability of
solvation model for dimethyl sulfoxide (DMSO). The
molecular coordinates are listed in the Supporting Infor-
mation (Section 1).
[
17]
[17,29]
the cationic forms : pK = 1.3 for MONO(OH),
a
[
17]
pKa1 = 0.2 and pKa2 = 2.6 for DPE(OH)2,
pKa1 = 1.3
and pKa2 = 3.5 for XAN(OH) (Figure 1B). It was found
2
4
| RESULTS AND DISCUSSION
that the cationic forms of MONO(OH) and DPE(OH)
2
react readily with water to form PB derivatives, while
The linkers for this study were chosen because they pro-
vide a variable degree of flexibility and also exhibit a suit-
able geometry to bring the two OH groups in close
proximity to each other. These kinds of linkers have been
used previously to construct covalently linked dimers for
the equivalent conversion of XAN(OH) required several
2
hours and elevated temperatures. Such slow conversion
indicates a high rigidity of the 9,9‐dimethylxanthene
based linker that introduces an undesirable barrier for
the interconversion between two important catalytic
[24]
[25]
oxygen reduction
or evolution
and singlet fission studies.
monomer MONO(OH) was used as a reference model
reaction catalysis,
intermediates. The dication of BP(OH) was found to be
2
[18]
[26–28]
redox switches,
The
chemically unstable in acidic medium (the UV‐vis
absorption signal decayed within 2‐3 hours), which
FIGURE 1 A, UV‐vis absorption spectra of XAN(OH)
dissolved in a small amount of acetonitrile followed by addition of water in large excess). B, pH‐dependent absorption of MONO(OH)
monitored at 378 nm), DPE(OH) (378 nm), and XAN(OH) (363 nm)
2 2
at different pH values (from pH 7 to pH 0; to prepare solutions, XAN(OH) was
(
2
2

ZORIC ET AL.
5 of 9
prevented us from evaluating the PB pK value of this
model compound. The instability of the C form of
compounds were calculated at the B3LYP/6‐311G*//
IEFPCM (DMSO) level of theory, and the results are sum-
marized in Table 1. In order to obtain the best starting
geometries for optimization, DFT calculations involving
energy scans were performed. Dihedral angle C6‐C7‐C8‐
C9 (rotation around C7‐C8 bond, Scheme 1) was changed
by 10° increments while the structure was optimized, and
energy recorded to obtain the energy diagram as a func-
tion of the dihedral angle. The minima at the energy dia-
gram were then used as starting structures for ground‐
state optimizations, while the maxima were used as the
starting structures for the TS calculations.
a
BP(OH) was not investigated further. It might involve
2
an intramolecular Friedel‐Crafts reactivity as was
[17]
observed previously for the DPE(OH) dication.
2
4.2 | Computational studies
The three model dimers can adopt three different config-
urations, namely In‐In, In‐Out, and Out‐Out, depending
on the orientation of the ─OH group in the molecule as
shown in Table 1. To evaluate the most stable conforma-
tion of DPE(OH) , XAN(OH) , and BP(OH) , relative
The optimized structures of all three In‐In conformers
indicate that the two ─OH groups are well positioned for
an O─O coupling reaction. The O···O distances in the
2
2
2
energies of three possible conformers in these model
TABLE 1 Optimized structures and relative energies for the three conformers (In‐In, In‐Out, and Out‐Out) and the TS for the model dimers
DPE(OH) XAN(OH) BP(OH)
2
2
2
In‐In
E
r
1.9
0.0
2.5
0.0
0.0
In‐Out
E
r
2.1
6.5
Out‐Out
E
r
12.8
7.5
TS
E
r
7.9
14.1
2.6·10
11.2
4.0·10
a
−1
6
2
4
k (s
)
9.3·10
Note. Calculations were performed at the B3LYP/6‐311G*/IEFPCM (DMSO) level of theory. Dashed lines indicate hydrogen bonds.
kbT −ΔG≠
a
Rate constants for interconversion between In‐In and In‐Out conformers were calculated using the Eyring equation: k ¼
e
RT , where k
b
is the Boltzmann
h
−
23
2
−2 −1
−34
m kg s ), ΔG≠ is the energy barrier for the noted rotation, and R is
2
−1
constant (1.38·10
m kg s
K
), T is the temperature, h is Planck constant (6.626·10
−1
the universal gas constant (8.314 J mol K ).

6
of 9
ZORIC ET AL.
−
1
−1
three conformers are as follows: 2.87, 2.81, and 2.71 Å for
DPE(OH) , XAN(OH) , and BP(OH) , respectively. Fur-
(7.9 kcal mol ), followed by BP(OH) (11.2 kcal mol ),
2
−
1
and XAN(OH) (14.1 kcal mol ). The TS structures of
2
2
2
2
thermore, the three In‐In conformers are stabilized by
the presence of an intramolecular hydrogen bond
between the two ‐OH groups. The hydrogen bond dis-
tances (H···O) and angles (O─H···O) indicate moderate
the DPE(OH) and XAN(OH) are stabilized by intramo-
2
2
lecular hydrogen bonds. The calculated TS energies were
used to evaluate the rates for interconversion between the
In‐In and In‐Out conformers and the obtained rate con-
[30]
2
6
−1
hydrogen bonding
having the shortest bond (1.76 Å), followed by XAN(OH)2
1.85 Å) and DPE(OH) (1.93 Å). The strongest hydrogen
in all three dimers with BP(OH)2
stants are found to be in the 10 to10
s
range
(Table 1). These rate constants indicate that the intercon-
version occurs on the μs to ms timescale, which might
have a profound effect on turnover frequencies.
(
2
bonding in BP(OH) is likely due to favorable proximity
2
of the two ─OH groups placed by the biphenyl linker.
Weak hydrogen bonds are also present in some of the
other conformers, and their parameters are listed in the
Supporting Information (Section 1, Table S1).
Overall, the calculations indicate that BP(OH)2
exhibits the most favorable energetics for the formation
of the In‐In conformer. The short biphenyl linker enables
the formation of a strong intramolecular hydrogen bond
between the two ‐OH groups of the In‐In conformer,
while the lack of oxygen atoms in the linker prevents
hydrogen bond stabilization of the undesired In‐Out con-
former. The TS energies for conformational interconver-
sion are relatively low, suggesting that the desired In‐In
conformer in all model compounds can be reached on
the μs to ms timescales.
Comparison of relative energies of the In‐In, In‐Out,
and Out‐Out conformers indicates that the most stable
[
17]
conformation of DPE(OH) is the In‐Out structure,
2
while XAN(OH) and BP(OH) adopt the desirable In‐In
2
2
structure as their most stable form. The stabilization of
the In‐In structure relative to the other conformers is
most pronounced for BP(OH) . The favorable energetics
2
in the BP(OH) structure are due to three effects: (a) the
2
In‐In conformer of BP(OH)2 is stabilized by a strong
intramolecular hydrogen bond (stronger than in
DPE(OH) and XAN(OH) ); (b) the In‐Out conformer of
4.3 | Crystal structures
2
2
[
17]
BP(OH) is not stabilized by hydrogen bonding, while
Single crystals of DPE(OH)2,
XAN(OH) , and BP(OH)
2 2
2
the same conformers in DPE(OH)2 and XAN(OH)2
exhibit hydrogen bonds between one of the ─OH groups
and the oxygen atoms of the linkers (O···H distances
were obtained by either vapor diffusion or by slow evap-
oration methods, and the corresponding crystal structures
are shown in Figure 2. In the solid state, only BP(OH)2
was found to adopt the desired In‐In conformation, while
DPE(OH) and XAN(OH) adopted In‐Out structures. The
1
.91 Å for DPE(OH) and 1.84 Å in XAN(OH) ); (c) the
2 2
Out‐Out conformer of BP(OH) is destabilized by unfavor-
2
2
2
able steric interactions between the two xanthenol units.
The barrier for interconversion between the three con-
formers was evaluated by performing a TS optimization
for the rotation around the C6‐C7‐C8‐C9 dihedral angle
In‐Out structures of DPE(OH) and XAN(OH) are stabi-
2
2
lized by two weak to moderate hydrogen bonds involving
the inward‐facing ─OH groups and either the O‐atom
present on the linker moiety or the O‐atom present on
the second xanthenol moiety. These hydrogen bonds have
also been predicted by DFT calculations (Tables S1 and
S3). However, DFT calculations predict that the lowest
(Table 1; see Scheme 1 for atom numbering). As expected,
the calculated TS energies reflect the rigidity of the
linkers, with DPE(OH)2 exhibiting the lowest barrier
FIGURE 2 Depictions of X‐ray structures of DPE(OH)
2 2 2
, XAN(OH) , and BP(OH) obtained from single crystals grown from saturated
dichloromethane/pentane or ethanol solutions. Dashed lines represent hydrogen bonding. Atom labels: O, red; C, gray; H, white

ZORIC ET AL.
7 of 9
energy conformer in XAN(OH) is an In‐In structure,
using 2D NMR spectra presented in Figures S2 to S10,
Section 3). The use of d6‐DMSO prevents the formation
of solute‐solute intermolecular hydrogen bonds, while
the intramolecular hydrogen bonds remain intact.
The comparison of chemical shifts of ─OH protons in
2
while the crystal structure indicates that XAN(OH) pre-
2
fers an In‐Out conformation. This may be due to addi-
tional stabilization by intermolecular hydrogen bonds
between the outward‐facing ─OH group and the π elec-
tron density of a neighboring phenyl ring and oxygen
atom (Figure S1). Similar stabilization effects were
[31–35]
model compounds indicates that XAN(OH) and BP(OH)
2
2
adopt In‐In conformations in d6‐DMSO solutions. Specifi-
cally, the ─OH protons of MONO(OH) and DPE(OH)2,
which are not expected to form intramolecular hydrogen
bonds, appear at relatively low chemical shifts (6.77 and
6.02 ppm, respectively) relative to the OH protons in
XAN(OH) and BP(OH) (8.29 and 7.54 ppm, respec-
observed in the crystal structure of DPE(OH) , where
2
the outward‐facing ─OH group formed four intermolecu-
[
17]
lar hydrogen bonds with neighboring phenyl rings.
BP(OH) attains its minimum energy In‐In conformation
2
in the crystal structure with the two oxygen atoms placed
at a distance of 2.68 Å. The In‐In conformer is stabilized
by an intramolecular hydrogen bond involving two
OH groups, as predicted by DFT calculations (Tables S1
and S3).
2
2
tively). These findings strongly indicate that XAN(OH)2
and BP(OH) form In‐In conformers in DMSO, where
2
─
intramolecular hydrogen bonding between two OH
groups can take place, leading to downfield‐shifted sig-
nals. The presence of downfield‐shifted signals also indi-
cates that no interconversion between In‐In, In‐Out, and
4
.4 | NMR studies
Out‐Out conformers of XAN(OH) and BP(OH) takes
place on the NMR timescale. These results are in agree-
ment with the calculated barriers for rotation (Table 1).
2 2
NMR spectroscopy was utilized to investigate the confor-
mational behavior of model dimers in solution. The con-
In the case of XAN(OH) , a number of weak NMR signals
2
formational analysis of DPE(OH) was reported in a
were observed in addition to the strong signals assigned to
the In‐In conformer (Figure 3). Meticulous purification of
the sample did not result in the disappearance of these
weak NMR signals, indicating that they are not associated
with sample impurities. We assign these peaks to a small
amount of an additional conformer (In‐Out or Out‐Out)
2
[17]
previous study,
which showed that the In‐In, In‐Out,
and Out‐Out conformers interconvert freely on the NMR
timescale. Those findings are consistent with the calcu-
6
−1
lated interconversion rate constant of k = 9.3·10 s
Table 1). In this study, similar investigations were
expanded to the XAN(OH) and BP(OH) dimers.
(
of XAN(OH) in solution. Unfortunately, the NMR signals
2
2
2
Figure 3 shows the NMR spectra of our model com-
pounds in d6‐DMSO (peak assignments were made
were too weak for efficient structure assignment. How-
ever, based on the calculated conformer energies
1
FIGURE 3 H NMR spectra of MONO(OH), DPE(OH)
2
, XAN(OH)
2
, and BP(OH)
2
in d6‐DMSO and their peaks assignments (proton
numbering is according to Scheme 1)

8
of 9
ZORIC ET AL.
1
FIGURE 4 H NMR data of diols in anhydrous d6‐DMSO (green, blue, and purple spectra for DPE(OH)
respectively) and after addition of one equivalent of D O per xanthenol unit (black spectra)
2 2 2
, XAN(OH) , and BP(OH) ,
2
presented in Table 1, it is very likely that the weak signals
appear due to the In‐Out conformer.
5 | CONCLUSIONS
To provide additional support for the In‐In conformer
assignment for XAN(OH) and BP(OH) models in solu-
This study shows how three linkers affect the relative
geometry and interconversion kinetics of alcohol units
in covalently linked dimers. The dimers containing
xanthene and biphenyl linkers were found to favor an
In‐In conformation in solution, while a more flexible
diphenyl ether linker exhibits a low barrier for conformer
interconversion. The In‐In orientation of two alcohol
groups is desirable for several applications of diols, such
as metal‐free oxygen evolution and reduction reactions.
2
2
1
tion, the H NMR experiments were performed using
partially deuterated ─OH groups. Previous studies have
shown that partial deuteration can be used to study
[36]
intramolecular hydrogen bonds.
If an intramolecular
hydrogen bond exists, then partial deuteration will gen-
erate two proton peaks, one arising from an OH···OH
species, another one coming from an OH···OD species
(inset structures in Figure 4). If, on the other hand, no
intramolecular hydrogen bonding takes place, the par-
tial deuteration will result in the presence of one atten-
uated NMR peak. In our experiment, the partial
deuteration of MONO(OH) (data not shown) and
ACKNOWLEDGEMENTS
This work is supported by National Science Foundation
(
NSF) (grant CHE‐1565971). The computational work
was performed using resources from the Ohio Supercom-
puter Center. The X‐ray diffractometer was funded by
NSF grant CHE 0087210, Ohio Board of Regents grant
CAP‐491, and Youngstown State University.
DPE(OH) (Figure 4) resulted in the attenuation of the
2
─
OH proton signal, without the appearance of a new
peak. This result is consistent with our previous report
that DPE(OH) freely interconverts between In‐In, In‐
2
[17]
Out, and Out‐Out conformers.
In contrast, partial
deuteration of BP(OH)2 and XAN(OH)2 caused the
appearance of new OH peaks, which is consistent with
the presence of intramolecularly hydrogen‐bonded In‐
In conformers. Overall, the NMR results are in excellent
agreement with the calculated conformer energies and
rate constants (Table 1), which predict that DPE(OH)2
rotates freely on the NMR timescale, while BP(OH)2
CONFLICT OF INTEREST
There are no conflicts to declare.
ORCID
Marija R. Zoric https://orcid.org/0000-0001-7296-0121
Varun Singh https://orcid.org/0000-0002-6453-4349
Ksenija D. Glusac https://orcid.org/0000-0002-2734-057X
and XAN(OH) are locked in the In‐In conformations.
2
These results are important for catalysis and indicate
that BP(OH)2 and XAN(OH)2 linkers are promising
motifs for oxygen evolution reaction (OER) dimer cata-
lysts. Electrochemical OER was attempted with model
dimers, but no catalysis was observed. Possible explana-
tion is the fact that proton‐coupled oxidation of these
alcohols is expected to take place in the pH = 14 to
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SUPPORTING INFORMATION
Additional supporting information may be found online
in the Supporting Information section at the end of the
article.
How to cite this article: Zoric MR, Singh V,
Zeller M, Glusac KD. Conformational analysis of
diols: Role of the linker on the relative orientation
of hydroxyl groups. J Phys Org Chem. 2019;e3975.
https://doi.org/10.1002/poc.3975